A follow‐up study of a Chinese family with Waardenburg syndrome type II caused by a truncating mutation of MITF gene

BACKGROUND: Waardenburg syndrome (WS) is a highly clinically and genetically heterogeneous disease. The core disease phenotypes of WS are sensorineuronal hearing loss and pigmentary disturbance, which are usually caused by the absence of neural crest cell‐derived melanocytes. At present, four subtypes of WS have been defined, which are caused by seven genes. Waardenburg syndrome type 2 (WS2) is one of the most common forms. Two genes, MITF and SOX10, have been found to be responsible for majority of WS2. METHODS: In this study, we performed a clinical longitudinal follow‐up and mutation screening for a Chinese family with Waardenburg syndrome type II. RESULTS: A diversity of clinical manifestations was observed in this WS2 family. In addition to the congenital hearing loss of most affected family members, progressive hearing loss was also found in some WS2 patients. A nonsense mutation of c.328C>T (p.R110X) in MITF was identified in all affected family members. This mutation results in a truncated MITF protein, which is considered to be a disease‐causing mutation. CONCLUSION: These findings offer a better understanding of the spectrum of MITF mutations and highlight the necessity of continuous hearing assessment in WS patients.